Continuous Molecular Monitoring Using Electrochemical Aptamer-Based Sensors: Remaining Challenges for Long-Term In Vivo Deployment.

In vivo continuous molecular monitoring represents a long-standing, transformative objective in medicine, with the potential to fundamentally reshape disease diagnostics, therapeutic decision-making, and long-term patient management by providing dynamic biochemical information that is currently inaccessible. Electrochemical aptamer-based biosensors offer a particularly promising and generalizable platform, as engineered aptamers can selectively bind diverse molecular targets and transduce binding-induced conformational changes into robust electrochemical signals. Recent studies have demonstrated encouraging progress toward extended in vivo operation, including early examples of week-scale functionality, highlighting the growing feasibility of this approach. Nevertheless, achieving robust and broadly applicable long-term in vivo deployment remains an ongoing challenge due to factors such as sensor degradation and limitations in fully integrated device architectures. To address these challenges, multiple strategies have emerged, including drift-canceling calibration, non-natural nucleic acids, antifouling coatings, nanoengineered electrodes, advanced immobilization and ultralow-power wireless systems, which are beginning to converge to enhance overall device performance. This review examines principles of aptamer-based biosensing, delineates mechanisms of signal degradation, and surveys emerging strategies for stability enhancement and system-level integration, outlining pathways toward longitudinal continuous molecular monitoring in personalized medicine.